Extracellular matrix (ECM)-based scaffolds, through their inherent bioactivity and molecular recognition signals, provide the ideal substrate for tissue engineering and regenerative applications. Collagen, the most abundant ECM protein, has proven itself to be a very versatile material with applications in many fields, including the leather and food industries, cosmetics, drug delivery, and tissue engineering. However, doubts persist about the optimal source of collagen for tissue engineering applications, given possible immunogenicity and disease transmission associated with animal sources and reduced bioactivity and availability of recombinant technologies. In this special edition, an attempt is made to elucidate the advantages of plant-derived human recombinant collagen and its applications in tissue engineering, particularly skin and wound healing. While results are promising, the widespread use of animal-derived collagen means that recombinant technologies may find applications in niche areas.